The goal of this project is to study the electrophysiological and anatomical changes which occur in human epileptic foci and in an animal model of the disease using the in vitro slice technique. Two distinct types of human epileptic foci will be studied: neocortical lesions and cases of medial temporal lobe sclerosis in which the hippocampus is the presumed focus. In addition, we will study the heat kindled rat model developed by Dr. de Lanerolle. There are two broad goals for the lesion studies. First, to determine the mechanisms underlying the hyperexcitability seen in the regions adjacent to lesions and second to determine whether cortex which is electrographically active but distant from an identified lesion has similar characteristics to that tissue found near a lesion. Electrographically quiet tissue taken from the edge of the resection will serve as an internal control. Possible mechanisms for the observed hyperexcitability include changes in the control of pH and K+ in the extracellular environment, or changes in the balance between inhibition and excitation. These possibilities will be tested both in situ and in vitro. For the hippocampal foci, the relationship between the entorhinal cortex and the hippocampal fields will be investigated using electrophysiological and anatomical techniques. We have developed a slice preparation whereby the connections between the entorhinal cortex and the hippocampus are maintained. We propose to examine the possibility that the entorhinal cortex forms and receives aberrant connections with both the dentate granule cells and with the few pyramidal cells which survive in this type of epilepsy. We will use tissue from the hippocampi of patients with temporal lobe lesions as comparison tissue. The extracellular environment will also be assessed in these cases. To date there are no animal models for medial temporal lobe sclerosis which completely mimic the human disease. Dr. de Lanerolle has developed the heat kindled rat model; the preliminary data collected to date on this animal model are promising. We will extend Dr. de Lanerolle's studies by examining the physiological characteristics of both the hippocampus and neocortex of these animals. These results will be compared with those from humans. These studies may provide information on any common mechanisms underlying these forms of human epilepsy.